This application for renewal of the California NeuroAIDS Tissue Network (CNTN) responds to RFA-MH-08-021. The CNTN is part of the National NeuroAIDS Tissue Consortium (NNTC) which includes sites at the Mt. Sinai School of Medicine, UCLA, and University of Texas Galveston. Consistent with the RFA's requirements, this application is in two parts: Part A (identical for all 4 applications) describes the overall aims and operations of the NNTC, including common protocols and shared scientific agendas. Part B is the Site specific application, which is described below. The CNTN's main objective has been to perform careful neuromedical, neuropsychiatric, and laboratory evaluations of persons with HIV so that these data can be linked to neuropathological information obtained from brain and other tissues of participants who die on study and consent to organ donation. This enables us to support research throughout the country by providing investigators with tissues, fluids, and data that will keep them to answer critical questions on the causes and possible treatment and prevention of neurologic disease in AIDS. To date CNTN has antemortem clinical information on 544 persons living with HIV and have analyzed brain and other tissues from 198 HIV+ persons. We have also banked tissues from 20 HIV uninfected persons for comparison study. As an active member of the NNTC, CNTN contributes data to the NNTC Coordinating Office, which has enabled NNTC to respond to 212 requests from various investigators. In this continuation phase CNTN plans to augment its resource mission with a scientific agenda, as envisioned in the RFA. Initial scientific analyses will focus on neuropathologic characteristics of immune reconstitution inflammatory syndrome, an exploration of the cellular basis and structural correlates of HIV leukoencephalopathy, mechanisms of early neuronal aging among persons with prolonged exposure to HIV and ARV treatment, and the role of viral drug resistance in HIV brain disease. Our resource contributions to the NNTC will include membership in the NNTC's Scientific Leadership Group, collaboration on NNTC-wide preliminary studies and QA activities, technical assistance in areas of CNTN's expertise, and continuing contribution of data from antemortem and postmortem evaluations. Part A: